Hepatitis B vaccine responsiveness and clinical outcomes in HIV controllers

Abstract

Background: Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied.

Methods and findings: In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naïve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23-5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15-1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35-0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1-1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0-0.76) versus 0.98 (95% CI 0.74-1.28) for vaccine responders and 0 (95% CI 0-2.22) versus 4.11 (95% CI 3.38-4.96) for non-responders, respectively.

Conclusions: HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC.

Figure 1. Kaplan-Meier plots demonstrating the time to AIDS or death for HIV controllers (HIC) compared to non-controllers by hepatitis B virus (HBV) vaccine antibody response status (A and B) and outcomes for non-controllers alone (C).

Among HBV vaccine responders (A) and non-responders (B), the time to AIDS or death was significantly longer for HIC compared to non-controllers (Log Rank P<0.001 for both). (C). Examination of non-controllers alone by HBV response status showed a longer time to AIDS or death for vaccine responders compared to non-responders (P<0.001). Anti-HBs, antibody to HBV surface antigen.